全文获取类型
收费全文 | 1216篇 |
免费 | 49篇 |
国内免费 | 75篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 48篇 |
妇产科学 | 24篇 |
基础医学 | 101篇 |
口腔科学 | 66篇 |
临床医学 | 179篇 |
内科学 | 307篇 |
皮肤病学 | 36篇 |
神经病学 | 27篇 |
特种医学 | 264篇 |
外科学 | 68篇 |
综合类 | 29篇 |
预防医学 | 56篇 |
眼科学 | 23篇 |
药学 | 64篇 |
中国医学 | 3篇 |
肿瘤学 | 42篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 3篇 |
2020年 | 7篇 |
2019年 | 14篇 |
2018年 | 18篇 |
2017年 | 11篇 |
2016年 | 17篇 |
2015年 | 19篇 |
2014年 | 24篇 |
2013年 | 27篇 |
2012年 | 43篇 |
2011年 | 30篇 |
2010年 | 47篇 |
2009年 | 55篇 |
2008年 | 29篇 |
2007年 | 61篇 |
2006年 | 31篇 |
2005年 | 26篇 |
2004年 | 15篇 |
2003年 | 18篇 |
2002年 | 21篇 |
2001年 | 28篇 |
2000年 | 22篇 |
1999年 | 15篇 |
1998年 | 84篇 |
1997年 | 71篇 |
1996年 | 61篇 |
1995年 | 52篇 |
1994年 | 47篇 |
1993年 | 44篇 |
1992年 | 29篇 |
1991年 | 17篇 |
1990年 | 27篇 |
1989年 | 43篇 |
1988年 | 42篇 |
1987年 | 36篇 |
1986年 | 26篇 |
1985年 | 30篇 |
1984年 | 19篇 |
1983年 | 14篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 14篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 16篇 |
1976年 | 15篇 |
1975年 | 13篇 |
1900年 | 2篇 |
排序方式: 共有1340条查询结果,搜索用时 140 毫秒
111.
Uemichi T; Liepnieks JJ; Alexander F; Benson MD 《QJM : monthly journal of the Association of Physicians》1996,89(10):745-750
Hereditary amyloidosis of an unusual form has been reported in two separate
kindreds; one was Polish-Canadian and the other was Irish- American (Am J
Med 1975; 59:121 and Trans Assoc Am Physicians 1981; 94:211). In both
kindreds, affected members developed hypertension and nephrotic syndrome
due to amyloidosis in their forties or fifties, but the genetic background
responsible for the condition has been left undetermined. To identify the
genetic defect in these kindreds, a portion of exon 5 of the fibrinogen
alpha-chain gene in members of these kindreds was examined for a mutation
by single-strand conformation polymorphism analysis and direct DNA
sequencing. DNA analyses revealed an A-->T transversion at the second
base of codon 526 of the fibrinogen alpha-chain gene in both of these
kindreds. Analysis of DNA polymorphisms in the fibrinogen alpha-chain gene
locus (TCTT repeat in intron 3, Rsal site in exon 5, and Taql site in the
3' flanking region of the gene) showed the haplotype B5-Rsal(+)-Taql(-) for
the Val 526 mutant gene in both kindreds studied here, as well as in two
kindreds previously described (J Clin Invest 1994; 93:731). The fibrinogen
alpha-chain gene mutation (Val 526) is the genetic defect responsible for
hereditary renal amyloidosis in these two kindreds, and the mutant genes in
the Val 526 kindreds may have been derived from a single founder.
相似文献
112.
Background
Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.”Objective
To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT).Materials and methods
We, retrospectively, reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18–70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response.Result
Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035).Conclusion
GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression. 相似文献113.
胶原海绵复合新生大鼠原代心肌细胞构建工程化心肌组织 总被引:2,自引:2,他引:2
目的:探索以胶原海绵为支架、新生大鼠原代心肌细胞为种子细胞,于体外构建工程化心肌组织的方法。方法:实验于2005-12/2006-11在解放军第四军医大学西京医院心内科实验室完成。Ⅰ型胶原海绵剪切成方形片状(2.0cm×1.4cm×0.2cm),经60Co照射消毒,于DMEM培养液中水化1h左右。另取1d龄SD大鼠心脏,剪成小碎块,然后用2.5g/L胰蛋白酶于37℃中消化,吸取上清至含胎牛血清的DMEM中,重复消化四五次,用差速贴壁法除去大部分成纤维细胞,将细胞沉淀用DMEM培养液以2×109L-1的密度悬浮备用。将上述的心肌细胞悬液1mL缓慢滴注于玻璃模型中的胶原海绵上,然后置于细胞培养中培养。肉眼及显微镜主要观察工程化心肌组织在培养期间的自发收缩情况,包括收缩的部位、强度、频率、一致性以及收缩随时间变化的情况。苏木精-伊红染色观察工程化心肌组织内胶原纤维的变化,细胞形态,胞核的形状及细胞之间的连接。免疫组织化学染色和透射电镜观察工程化心肌组织片的形态和功能。结果:①细胞接种于胶原海绵上1d后,细胞/胶原复合物的凝胶化过程基本完毕,体积保持恒定,维持至培养结束,第3天细胞/胶原复合物局部出现点片状自发收缩,第5天整个细胞/胶原复合物出现同步化自发收缩,收缩频率61~199次/min。2周后37.5%的工程化心肌组织的自发收缩活动减弱,但75%的工程化心肌组织的自发收缩活动持续至培养结束。②苏木精-伊红染色、免疫组织化学染色和透射电子显微镜显示,工程化心肌组织内细胞间连接广泛存在,细胞多呈纵向分布,胞核呈长圆形,胞浆内α-肌节肌动蛋白阳性,胞内肌原纤维排列整齐,可见到心肌特异性的肌小节结构和Z线,多数细胞具有分化的心肌细胞表型。结论:用新生大鼠原代心肌细胞为种子细胞、以Ⅰ型胶原海绵为支架材料,构建出的工程化心肌组织,于体外可长时间持续自发收缩,该细胞/胶原复合物的形态结构与生理功能均类似于成熟大鼠心肌组织。 相似文献
114.
目的:介绍言语流畅性的测量工具,考察言语流畅性与记忆之间的关系,探讨言语流畅性的神经生理基础。资料来源:应用计算机检索Sciencedirect 1975-07/2005-05中与言语流畅性相关的文献,检索词为“verbal fluency”,限定文章语言种类为英文。资料选择:对资料进行初审,选取文章标题中含有“verbal fluency”的英文文献。纳入标准:①对言语流畅性测量任务的研究。②对言语流畅性与记忆的研究。③对言语流畅性神经生理基础的研究。资料提炼:共收集到651篇关于言语流畅性的文章,纳入30篇用于本综述。资料综合:测量言语流畅性的任务主要分为简单任务(包括音位流畅性任务和语义流畅性任务)与复杂任务(包括可能工作、替代使用、草拟、推断、物品制作以及新的使用方法等)。言语流畅性任务的完成主要涉及到记忆搜索的过程,另外,精细组织的语义网络系统对于言语流畅性任务来说也是非常重要的。言语流畅性的神经生理基础包括了总体基础,前额叶,海马以及大脑两半球的不对称性。结论:言语流畅性作为人类语言基本技能的一项指标,对语言认知研究具有极其重要的意义。它不仅是神经心理研究的一项非常重要的检测和诊断指标,也是一种研究人类心理的非常有用的研究工具,是探索人类语言与认知、创造之迷进而探索人类意识之迷的钥匙。 相似文献
115.
目的:观察碱性成纤维细胞生长因子对大鼠脑出血后出血灶周围脑组织和出血侧海马bax、bcl-2基因表达的影响,探讨神经营养因子对神经细胞调亡的调控。方法:实验于2006-01/10在广西医科大学医学科学实验中心完成。①取成年清洁级Wistar大鼠72只,雌雄各半,体质量250g左右。②采用脑内囊注射胶原酶建立大鼠脑出血模型,动物于苏醒后按Bederson法进行神经病学评分,评分>3分后入选本实验,入选72只大鼠随机抽签法分为3组,每组24只。碱性成纤维细胞生长因子组按8μg/kg剂量肌肉注射,1次/d;生理盐水组肌肉注射等剂量的生理盐水,1次/d;模型组不作任何干预。③每组分别于干预后1,3,7d随机抽取8只大鼠,麻醉状态下取出血灶周围脑组织和出血侧海马,采用半定量反转录-聚合酶链反应检测调亡调控基因bax mRNA,bcl-2mRNA的表达。结果:在建立脑出血模型中共5只大鼠死亡,随后对死亡动物进行解剖,发现脑内血肿量过大,致脑疝形成而导致死亡,后随机补充动物。72只大鼠进入结果分析。①血肿周围脑组织bax mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组血肿周围脑组织bax mRNA表达比生理盐水组明显减少(3d:0.54±0.19,0.76±0.23,P<0.05;7d:0.45±0.19,0.71±0.16,P<0.01)。②血肿周围脑组织bcl-2mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组的血肿周围脑组织bcl-2mRNA表达比生理盐水组明显增高(3d:0.68±0.25,0.39±0.19,P<0.05;7d:0.80±0.21,0.48±0.18,P<0.01)。③出血侧海马bax mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bax mRNA表达比生理盐水组均明显减少(3d:0.54±0.18,0.70±0.11;7d:0.43±0.24,0.69±0.18,P均<0.05)。④出血侧海马bcl-2mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bcl-2mRNA表达比生理盐水组均明显增多(3d:0.66±0.11,0.50±0.15;7d:0.72±0.12,0.52±0.22,P均<0.05)。结论:碱性成纤维细胞生长因子能调节凋亡相关基因,提高大鼠脑出血后大脑脑组织和海马bcl-2mRNA的表达,降低bax mRNA的表达。 相似文献
116.
Vasopressin stimulation of adrenocorticotropin hormone (ACTH) in humans. In vivo bioassay of corticotropin-releasing factor (CRF) which provides evidence for CRF mediation of the diurnal rhythm of ACTH. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The Journal of clinical investigation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R A Salata D B Jarrett J G Verbalis A G Robinson 《The Journal of clinical investigation》1988,81(3):766-774
The diurnal response of ACTH release to intravenously administered arginine vasopressin was tested in normal volunteers given consecutively moderate doses of vasopressin every 15 min (0.1, 0.3, 1.0, and 3.0 IU) at 2200 h and again at 0700 h (PM/AM). This protocol was repeated 4 wk later with the times reversed (AM/PM). A dose-related increase in ACTH secretion was observed in all subjects. When the AM response of the AM/PM protocol was compared with the PM response of the PM/AM protocol, the release of ACTH was greater in the morning (P less than 0.05) as evaluated by the following criteria: peak value of ACTH (129.9 +/- 30.4 pg/ml in the AM vs. 57.1 +/- 20.2 in the PM); area under the curve (689 in the AM vs. 259 in the PM); and, sensitivity of the ACTH dose-response curve (first significant increase in ACTH with 1 IU of vasopressin in the AM but not significant even after 3 IU in the PM). In addition, when the AM vasopressin testing followed a previous evening stimulation (PM/AM protocol), there was a blunted ACTH response compared with the AM/PM protocol. Corticotropin-releasing factor (CRF) is probably the major ACTH secretagogue, but since vasopressin acts synergistically with CRF to produce an augmented release of ACTH, we suggest that the ACTH response to administered vasopressin depends upon the ambient endogenous level of CRF. We interpret our data and published data that CRF produces a lesser release of ACTH in the AM as follows: in the morning endogenous CRF is high and administered CRF produces little further release of ACTH, but administered vasopressin acting synergistically with high endogenous CRF causes a greater release of ACTH; conversely, in the evening endogenous CRF is low and administered CRF causes a greater release of ACTH, but vasopressin (a weak secretagogue by itself) gives a low ACTH response. We conclude that vasopressin stimulation of ACTH secretion can be used as an in vivo bioassay of endogenous CRF, and that there is a diurnal rhythm of CRF in hypophyseal portal blood. 相似文献
117.
The mouse monoclonal antibody M2A1 of IgG1 class, which is highly specific for blood group M antigen, was obtained and characterized by means of hemagglutination, enzyme-linked immunosorbent assay, immunoblotting, and inhibition assays. The use of modified M glycoprotein preparations for inhibition tests and of variant McN and Henshaw red cell membranes for immunoblotting showed that M2A1 recognized an epitope including the NH2-terminal serine and sialic acid residues of glycophorin A, whereas the fifth glycine residue was not involved. The reactivity of the antibody with M antigen was distinctly dependent on ionic strength and pH; the optimum was at pH 8 to 9. The alpha-amino group of terminal serine residue was not necessary for the reaction with M2A1 antibody, and the results obtained suggested that the positive charge of this group contributed to decreasing antigen-antibody reactions at pH below 8. The reaction of the antibody with blood group N antigen was not detectable in any of the assays used. 相似文献
118.
Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid 总被引:9,自引:0,他引:9
Ward M; McNulty H; McPartlin J; Strain JJ; Weir DG; Scott JM 《QJM : monthly journal of the Association of Physicians》1997,90(8):519-524
Elevated plasma homocysteine, an independent risk factor for cardiovascular
disease (CVD) can be lowered by administration of pharmacological doses of
folic acid. The effect of lower doses in apparently normal subjects is
currently unknown but is highly relevant to the question of food
fortification. Healthy male volunteers (n = 30) participated in a chronic
intervention study (26 weeks). Folic acid supplements were administered
daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms
(6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected
before, during and 10 weeks post intervention were analysed for plasma
homocysteine, serum and red- cell folate levels. Results, expressed as
tertiles of baseline plasma homocysteine concentration, showed significant
(p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83
mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low
tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84
mumol/l, no significant response was observed. Of the three folic acid
doses, 200 micrograms appeared to be as effective as 400 micrograms, while
100 micrograms was clearly not optimal. There is thus a minimal level of
plasma homocysteine below which folic acid has no further lowering effect,
probably because an optimal folate status has been reached. A dose as low
as 200 micrograms/day of folic acid is effective in lowering plasma
homocysteine concentrations in apparently normal subjects. Any public
health programme for lowering homocysteine levels, with the goal of
diminishing CVD risk, should not be based on unnecessarily high doses of
folic acid.
相似文献
119.
BACKGROUND AND OBJECTS: Lipids with platelet activating factor (PAF)-like activity in supernatant of packed red blood cells (PRBC) cause priming of the neutrophil respiratory burst. This effect increases with length of storage. Washing of PRBC has been considered as a means to eliminate this effect; however, the role of the cellular component was not evaluated independently of the supernatant. The source of the inflammatory lipids of the supernatant is likely to be cell membranes altered during ageing in storage and therefore, washing will not eliminate neutrophil priming caused by transfusion of aged PRBC units. The ability of washed PRBC to prime mononuclear cells for another known effect of PAF, the production of IL-8, and the probability that this lipid activity is present on microparticles in PRBC supernatant were also investigated. MATERIALS AND METHODS: At collection 10 units of whole blood were split into two equal aliquots one filtered and one unfiltered. PRBC were prepared and stored at 4 degrees C in CPD-AS5. Each week, fresh neutrophils were incubated with samples of washed PRBC and fixed. Change in CD11b, a marker known to increase on the surface of primed neutrophils, was determined by flow cytometry. To determine whether neutrophil priming ability of PRBC supernatant is contained on microvesicles, centrifuged and uncentrifuged supernatant samples were incubated with fresh neutrophils and change in CD11b expression was determined. Plasma IL-8 levels were also measured after exposure of monocytes from fresh whole blood to filtered and unfiltered washed PRBC with and without the addition of fMLP. RESULTS: Washed PRBC caused a 50-116% increase in CD11b neutrophil surface expression over baseline expression. Filtration of whole blood at collection reduced this CD11b up-regulation by 25-34%. Reduction of priming ability by filtration began on the day of collection and persisted for the storage life of the units. Centrifugation resulted in a reduction of CD11b up-regulation of 11-28% compared with unspun supernatant. Incubation of unfiltered PRBC resulted in priming of mononuclear leukocytes for IL-8 production with a 73-109% increase over baseline, but no increase over baseline was seen for incubation with filtered blood. CONCLUSION: Washing does not eliminate the ability of PRBC units to prime neutrophils and mononuclear cells, because the cellular component of PRBC, in addition to the supernatant, induces priming. Leukodepletion filters significantly reduce these effects compared with unfiltered PRBC. The in vitro beneficial effect of filtration lasts for the shelf life of 42 day units. The ability of PRBC supernatant to prime neutrophils is present on microvesicles. 相似文献
120.
Konrad Salata Muzammil Syed Mohamad A. Hussain Rachel Eikelboom Charles de Mestral Subodh Verma Mohammed Al-Omran 《Journal of vascular surgery》2018,67(2):629-636.e2